Method and Model Development Supporting Vaccines and Therapeutics Against Viral and Bacterial Pathogens and Toxins

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 3007

Special Issue Editor


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Guest Editor
Battelle Biomedical Research Center, West Jefferson, OH 43162, USA
Interests: virus host

Special Issue Information

Dear Colleagues,

The advancement of vaccine and therapeutic products to combat diseases caused by viruses, bacteria, and toxins requires the development of methods and models capable of testing the intended mechanisms and efficacy of novel products. It is also necessary to confirm that these products work in relevant models of the targeted disease and show their potential benefit over existing products. This Special Issue, entitled “Method and Model Development Supporting Vaccines and Therapeutics Against Viral and Bacterial Pathogens and Toxins”, has a broad scope and aims to present recent research on these key aspects of product development. Some of its focal points include, but are not limited to, the following: 

  • Novel in vitro methods for evaluating the intended mechanisms and efficacy of vaccines or therapeutics;
  • Method maturation through validation to support studies of products;
  • Unique approaches to method development, qualification, and validation, including statistical analyses;
  • Development of microphysiological systems to test vaccines and therapeutics;
  • Animal model development and characterization;
  • Testing novel products using developed methods and models.

Dr. Chris M. Cirimotich
Guest Editor

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Keywords

  • vaccines
  • animal model
  • microphysiological

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Published Papers (3 papers)

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Research

18 pages, 9382 KiB  
Article
A Novel In Vitro Primary Human Alveolar Model (AlveolAir™) for H1N1 and SARS-CoV-2 Infection and Antiviral Screening
by Cindia Ferreira Lopes, Emilie Laurent, Mireille Caul-Futy, Julia Dubois, Chloé Mialon, Caroline Chojnacki, Edouard Sage, Bernadett Boda, Song Huang, Manuel Rosa-Calatrava and Samuel Constant
Microorganisms 2025, 13(3), 572; https://doi.org/10.3390/microorganisms13030572 - 3 Mar 2025
Viewed by 976
Abstract
Lower respiratory infections, mostly caused by viral or bacterial pathogens, remain a leading global cause of mortality. The differences between animal models and humans contribute to inefficiencies in drug development, highlighting the need for more relevant and predictive, non-animal models. In this context, [...] Read more.
Lower respiratory infections, mostly caused by viral or bacterial pathogens, remain a leading global cause of mortality. The differences between animal models and humans contribute to inefficiencies in drug development, highlighting the need for more relevant and predictive, non-animal models. In this context, AlveolAir™, a fully primary in vitro 3D human alveolar model, was characterized and demonstrated the sustained presence of alveolar type I (ATI) and type II (ATII) cells. This model exhibited a functional barrier over a 30-day period, evidenced by high transepithelial electrical resistance (TEER). These findings were further validated by tight junctions’ confocal microscopy and low permeability to Lucifer yellow, confirming AlveolAir™ as robust platform for drug transport assays. Additionally, successful infections with H1N1 and SARS-CoV-2 viruses were achieved, and antiviral treatments with Baloxavir and Remdesivir, respectively, effectively reduced viral replication. Interestingly, both viruses infected only the epithelial layer without replicating in endothelial cells. These findings indicate AlveolAir™ as a relevant model for assessing the toxicity and permeability of xenobiotics and evaluating the efficacy of novel antiviral therapies. Full article
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9 pages, 211 KiB  
Article
Performance of Urine Reagent Test Strips in Detecting Schistosoma haematobium Infection in Individual and Pooled Urine Samples
by Abraham Degarege, Berhanu Erko, David M. Brett-Major, Bruno Levecke, Abebe Animut, Yohannes Negash, M. Jana Broadhurst, Tzeyu Michaud and Christopher R. Bilder
Microorganisms 2025, 13(3), 510; https://doi.org/10.3390/microorganisms13030510 - 26 Feb 2025
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Abstract
This study evaluated the performance of urine reagent strips (URSs) in detecting Schistosoma haematobium infection in individual and pooled urine samples. Between June 2022 and April 2023, 2634 urine samples (10 mL each) from school-age children (5–15 years) in 15 villages across Ethiopia’s [...] Read more.
This study evaluated the performance of urine reagent strips (URSs) in detecting Schistosoma haematobium infection in individual and pooled urine samples. Between June 2022 and April 2023, 2634 urine samples (10 mL each) from school-age children (5–15 years) in 15 villages across Ethiopia’s Afar, Benishangul-Gumuz, and Gambella regions were tested using urine filtration microscopy (UFM) and URSs for blood, a marker of S. haematobium eggs. Pooled samples from 5, 10, 20, and 40 individuals (one positive, others negative) were examined with both methods. UFM results were used to calculate URSs’ sensitivity, specificity, and predictive values for detecting infection. A total of 2634 children were screened for S. haematobium infection. UFM detected S. haematobium eggs in 370 samples, while URSs identified infection in 414 children. URSs showed 64% sensitivity and 92% specificity for individual samples. The positive and negative predictive values for individual samples were 57% and 94%, respectively. Sensitivity for pooled samples ranged from 47% (pools of 40) to 53% (pools of 20). In pools with one positive sample, URSs misclassified 220 (50%), 109 (49.5%), 52 (47.0%), and 28 (50.9%) pools as negative for S. haematobium eggs for pool sizes 5, 10, 20, and 40, respectively. Sensitivity for individual samples was higher in children with heavy infection (92.5%) compared to light infection (55.9%), and sensitivity in pooled samples increased with infection intensity (p < 0.001). In conclusion, URSs may misclassify S. haematobium infection in children when samples are examined individually or in pools, potentially leading to unnecessary treatment or missed cases. However, URSs shows promise as a screening tool for detecting S. haematobium infection in areas with high infection intensity. Full article
17 pages, 3814 KiB  
Article
Evaluation of the Anti-Mycobacterial and Anti-Inflammatory Activities of the New Cardiotonic Steroid γ-Benzylidene Digoxin-15 in Macrophage Models of Infection
by Daniel Wilson A. Magalhães, Maria Gabriella S. Sidrônio, Noêmia N. A. Nogueira, Deyse Cristina Madruga Carvalho, Maria Eugênia G. de Freitas, Ericke Cardoso Oliveira, Gustavo F. de Frazao Lima, Demétrius A. M. de Araújo, Cristoforo Scavone, Thalisson Amorim de Souza, José Augusto F. P. Villar, Leandro A. Barbosa, Francisco Jaime Bezerra Mendonça-Junior, Valnês S. Rodrigues-Junior and Sandra Rodrigues-Mascarenhas
Microorganisms 2025, 13(2), 269; https://doi.org/10.3390/microorganisms13020269 - 25 Jan 2025
Cited by 2 | Viewed by 1253
Abstract
Cardiotonic steroids modulate various aspects of the inflammatory response. The synthetic cardiotonic steroid γ-benzylidene digoxin 15 (BD-15), a digoxin derivative, has emerged as a promising candidate with potential immunomodulatory effects. However, its biological activity remains largely unexplored. This study investigated the anti-mycobacterial and [...] Read more.
Cardiotonic steroids modulate various aspects of the inflammatory response. The synthetic cardiotonic steroid γ-benzylidene digoxin 15 (BD-15), a digoxin derivative, has emerged as a promising candidate with potential immunomodulatory effects. However, its biological activity remains largely unexplored. This study investigated the anti-mycobacterial and anti-inflammatory effects of BD-15 in an in vitro macrophage infection model with Mycobacterium spp. Unlike digoxin, which showed significant toxicity at higher concentrations, BD-15 exhibited no cytotoxicity in RAW 264.7 cells (a murine macrophage cell line). Both compounds were evaluated in Mycobacterium smegmatis-infected RAW 264.7 cells, reducing bacterial burden without direct bactericidal activity. Additionally, both modulated pro-inflammatory cytokine levels, notably by decreasing tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels. BD-15 specifically reduced NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) inflammasome expression and increased interleukin-10 (IL-10) production. Notably, BD-15 reduced colony-forming unit (CFU) counts in Mycobacterium tuberculosis-infected RAW 264.7 cells. Toxicity assays in HepG2 cells (a human liver cancer cell line) showed that BD-15 had minimal hepatotoxicity compared to digoxin, and both demonstrated negligible acute toxicity in an Artemia salina bioassay. These findings revealed the immunomodulatory effects of cardiotonic steroids in a bacterial infection model and highlighted BD-15 as a safer alternative to digoxin for therapeutic applications. Full article
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